The occurrence of vasoactive intestinal polypeptide (VIP), peptide histidine methionine (PHM) and peptide histidine valine (PHV) in the human female genital tract was studied by means of radioimmunoassay in combination with gel chromatography. In addition, the effect of PHV on genital smooth muscle activity was investigated in vitro and compared to that of VIP. Immunoreactive VIP, PHM and PHV were present in all regions of the human female genital tract, the highest concentrations being measured in the vagina and the uterine cervix. The peptides displayed similar regional distribution and as expected from the structure of the VIP precursor molecule in which the examined peptides are contained, the molar ratio of VIP to the total PHM/PHV immunoreactivity was close to 1:1. In all regions PHV constituted 50-70% of the total PHM/PHV immunoreactivity indicating that the dibasic conversion site after PHM was uncleaved. VIP and PHV were found to be equipotent relaxants of the smooth muscle from the Fallopian tube and the myometrium. The present study indicates that PHV like PHM and VIP may act as a neurotransmitter in the human female genital tract and thus participate in the local nervous control of the reproductive functions.